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Issue 1, 2019
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Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds

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Abstract

A series of novel indazole–pyrone hybrids were synthesized by a one pot reaction between N-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2H-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained in good to excellent yields (72–92%) and characterized by NMR and single crystal X-ray diffraction. Nineteen compounds were tested in vitro against both Leishmania donovani (MHOM/ET/67/HU3, also called LV9) axenic and intramacrophage amastigotes. Among all, five compounds showed anti-leishmanial activity against intracellular L. donovani with an IC50 in the range of 2.25 to 62.56 μM. 3-(1-(3-Chloro-2-ethyl-2H-indazol-6-ylamino)ethylidene)-6-methyl-3H-pyran-2,4-dione 6f was found to be the most active compound for axenic amastigotes and intramacrophage amastigotes of L. donovani with IC50 values of 2.48 ± 1.02 μM and 2.25 ± 1.89 μM, respectively. However, the cytotoxicity of the most promising compound justifies further pharmacomodulations.

Graphical abstract: Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds

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Publication details

The article was received on 24 Sep 2018, accepted on 15 Nov 2018 and first published on 19 Nov 2018


Article type: Research Article
DOI: 10.1039/C8MD00475G
Citation: Med. Chem. Commun., 2019,10, 120-127

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    Synthesis and biological evaluation against Leishmania donovani of novel hybrid molecules containing indazole-based 2-pyrone scaffolds

    M. El Ghozlani, L. Bouissane, M. Berkani, S. Mojahidi, A. Allam, C. Menendez, S. Cojean, P. M. Loiseau, M. Baltas and E. M. Rakib, Med. Chem. Commun., 2019, 10, 120
    DOI: 10.1039/C8MD00475G

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